反应详情

A mixture of 412 mg (2.27 mmol, 1.1 eq) of C—(R)-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine (prepared in EXAMPLE 50, steps 1 to 4) and 700 mg (2.07 mmol, 1 eq) of 6-chloro-3-(2-ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxy-N,N-dimethylbenzamide in 45 ml of methanol was stirred at ambient temperature for 3 days. The methanol was evaporated off and the residue was taken up with ethyl acetate and washed with a 1 M aqueous sodium dihydrogen phosphate solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. The residue (0.90 g) was chromatographed on silica gel (80 g prepacked column, eluent dichloromethane/methanol, from 0 to 10% of methanol). 520 mg of 6-chloro-2-hydroxy-N,N-dimethyl-3-(2-{[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}-3,4-dioxocyclobut-1-enylamino)benzamide were obtained in the form of an ochre solid. Yield=53%. Mp=165-167° C.

1. customThe methanol was evaporated off
2. washwashed with a 1 M aqueous sodium dihydrogen phosphate solution
3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue (0.90 g) was chromatographed on silica gel (80 g prepacked column, eluent dichloromethane/methanol, from 0 to 10% of methanol)